The effect of interaction of selected, specific acting cancer chemotherapeutic agents with radiation on the cell cycle kinetics and the survival of the Chinese hamster ovary (CHO) fibroblast will be documented. Emphasis will be placed on determining: transition points for drug action in late S and G2; drug time dependence for inhibition of cell division; analyzing entry into S-phase of cells which were refractory to or recovered from an initial treatment; survival of refractor and recovered cells after treatment during the next cycle. Both major goals, kinetics and survival, will be approached by using the mitotic selection procedure for cell cycle analysis. After the initial treatment the continuous selection of mitotic cells will separate those cells which were not immediately affected by radiation or drug challenge from those which were affected; referred to as refractory and recovered cells; respectively. In addition, the rate of cell selection after the initial treatment is a precise measure of cell progression. These refractory and recovered cells will then be challenged in the following G1, S or G2 with appropriately chosen drugs or radiation. Various radiation and drug doses will be employed so that dose survival curves, cell cycle dependent survival, and cell kinetics may be established. From the survival curves the parameters Do, Dg and n will be determined as a function of the combined treatment and position in the cell cycle. Emphasis will be placed on establishing the optimal sequence of drug and radiation sequences to reduce reproductive integrity. Comparison of these results with current clinical combined modality protocols will aid in the development of a rational in vitro approach to combined therapeutic modality therapy.